炎症性肠病与结膜炎的遗传关联和因果效应。

BACKGROUND: Inflammatory bowel disease (IBD) is often clinically associated with conjunctivitis, which may result from genetic associations and causal effects. METHODS: Genetic correlations were investigated through the genome-wide association study (GWAS) data on IBD and conjunctivitis using the linkage disequilibrium score regression (LDSC) and heritability estimated in summary statistics (HESS). The causal effect analysis was performed using four methods of Mendelian randomization (MR) and the genetic risk loci common to both diseases were identified by the statistical method of conditional/conjoint false discovery rate (cond/conjFDR), followed by genetic overlap analysis. Finally, a multi-trait GWAS analysis (MTAG) was performed to validate the identified shared loci. RESULTS: IBD (including CD and UC) and conjunctivitis showed a significant overall correlation at the genomic level; however, the local correlation of IBD and CD with conjunctivitis was significant and limited to chromosome 11. MR analysis suggested a significant positive and non-significant negative correlation between IBD (including CD and UC) and conjunctivitis. The conjFDR analysis confirmed the genetic overlap between the two diseases. Additionally, MTAG was employed to identify and validate multiple genetic risk loci. CONCLUSION: The present study provides evidence of genetic structure and causal effects for the co-morbidity between IBD (both CD and UC) and conjunctivitis, expanding the epidemiologic understanding of the two diseases.

背景：炎症性肠病（IBD）常与结膜炎临床相关，这可能源于遗传关联和因果效应。

方法：利用连锁不平衡得分回归（LDSC）和汇总统计数据中估计的遗传力（HESS），通过 IBD 和结膜炎的全基因组关联研究（GWAS）数据，研究遗传相关性。采用孟德尔随机化（MR）的四种方法进行因果效应分析，并通过条件/联合虚假发现率（cond/conjFDR）的统计方法识别两种疾病共有的遗传风险位点，然后进行遗传重叠分析。最后，进行多性状 GWAS 分析（MTAG）来验证鉴定出的共享位点。

结果：IBD（包括 CD 和 UC）和结膜炎在基因组水平上表现出显著的总体相关性；然而，IBD 和 CD 与结膜炎的局部相关性显著，且仅限于 11 号染色体。MR 分析表明 IBD（包括 CD 和 UC）与结膜炎之间存在显著的正相关和非显著的负相关。conjFDR 分析证实了这两种疾病的遗传重叠。此外，MTAG 用于鉴定和验证多个遗传风险位点。

结论：本研究为 IBD（包括 CD 和 UC）和结膜炎共病的遗传结构和因果效应提供了证据，扩展了对这两种疾病的流行病学理解。